We propose to use a unique experimental model, in which we can identify the selected preovulatory follicle in rhesus monkeys with confidence and induce atresia with certainty, to develop more detailed information about the regulation of follicular growth and atresia in primates as studied in vivo and in vitro, and to relate the adequacy of luteal function to imposed variations in follicular development. Specific hypotheses to be tested are: (1) estrogen induces atresia of the follicle selected for ovulation by a direct action on the ovary, (2) currently-accepted putative markers of atresia can be validated by observing the intrafolliculr changes which occur in estrogen-induced atretic follicles, (3) atresia of the follicle selected for ovulation need not be an all-or-none phenomenon, but may be graded in a dose-related manner, (4) inadequate or interrupted follicular development leads to inadequate luteal function. In vivo experiments will utilize cyclic monkeys, treated with estrogen administered in graded amounts and durations from Silastic capsules placed locally at the ovary or peripherally. Results will be evaluated by laparoscopic observations and radioimmunoassay for serum concentrations of FSH, LH, estradiol-17B, and progesterone. Rescue of follicles subjected to atresia-including regimens will be attempted with the use of hMG. Material obtained by aspirating follicles will be studied morphologically and incubated in vitro to validate suggested markers of atresia, and to provide clues about intrafollicular mechanisms. In animals which ovulate following in vivo manipulations, luteal function will be assessed by laparoscopy and serum concentrations of progesterone to determine if suppressed follicular development dictates reduced luteal capacity and infertility. The findings will contribute to our long-term goals of understanding the controlling mechanisms which dictate that most follicles will undergo atresia, and why those that ovulate are spared from this fate. This understanding will provide the basis for more effective methods to regulate fertility and infertility in women.